Treatment of skin disorders

ABSTRACT

The present invention provides a method and composition for treating skin disorders, skin pathologies and pruritus, which includes applying a compound of formula (I) in a suitable formulation to the affected area.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation-in-part of patent applicationSer. No. 09/389,837 filed Sep. 3, 1999 in the United States Patent andTrademark Office.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[0002] Not Applicable

BACKGROUND OF INVENTION

[0003] The milieu of the skin is normally of acidic pH, i.e. the stratumcorneum layer of the human skin is normally acidic. The stratum corneumis the thin outer cornified lipophilic epidermal layer of the skin,which functions as a barrier to the external environment. It is nowgenerally accepted that this outer layer of the skin has a natural pH inthe range of 4.0 to 6.0, normally 5.0. Ten to fifteen micrometers belowthe stratum corneum, the pH quickly rises to a neutral pH of 7.0.

[0004] Within the thin stratum corneum resides a diverse array ofhydrolytic, proteolytic, esterifying, and lipid active enzymes which allappear to function optimally in an acidic range of pH 4.5-6.0, which istypical of this layer. Disruption of the pH of this layer by a vastarray of etiologies is associated with numerous well-describedpathologic entities. In other words, abnormally high pH, or abnormalalkalization, of the skin is often associated with many pathologicdermatological states.

[0005] For example, abnormal alkaline surface pH has been noted inatopic dermatitis. Atopic dermatitis is a chronic, itching, superficialinflammation of the skin, frequently associated with related disorders,such as hay fever and asthma. Atopic dermatitis may begin in the firstfew months of life, with red, weeping, crusted lesions on the face,scalp, diaper area and extremities. In older children or adults, it maybe more localized and chronic. Although the dermatitis often improves byage 3 or 4, exacerbations are common during childhood, adolescents oradulthood. Itching is a constant feature, and consequent scratching andrubbing lead to an itch-scratch-rash-itch cycle.

[0006] Another pathology generally associated with abnormally highalkalinity of the skin is ichthyosis. Ichthyosis is a symptom in severalrare hereditary syndromes and in several systematic disorders. Itusually occurs in the lower legs of middle aged or older patients, mostoften in cold weather and in patients who bathe frequently. Mild tomoderate itching may exist in an associated dermatitis due to detergentsor other irritants. Xeroderma is the mildest form of ichthyosis.

[0007] Another example is seborrheic dermatitis. Seborrheic dermatitisis an inflammatory scaling disease of the scalp, face and occasionallymore generalized areas. Onset in adults is gradual, and the dermatitisusually is apparent only as dry or greasy diffused scaling of the scalp(dandruff) with variable itching. In severe disease, yellow-red scalingpapules appear along the hairline, behind the ears, and externalauditory canals, on the eyebrows, on the bridge of the nose, thenasolabial folds, and over the sternum. Dry yellow crusting andconjunctival irritation may also be present. Neonates under one monthold may develop seborrheic dermatitis, with thick, yellow, crusted scalplesions, fissuring and yellow scaling behind the ears and red facialpapules. Newborns may also have an associated stubborn diaper rash,while older children may develop thick, tenacious, scaly plaques in thescalp that may measure 1 to 2 centimeters in diameter. Very rarely, ininfants or adults, the condition may become generalized.

[0008] Contact dermatitis, another example of a skin disorder associatedwith abnormally basic skin, is characterized as an acute or chronicinflammation, produced by substance contact with the skin. Contactdermatitis may be caused by marginal irritants such as soap, detergents,acetone or even water. It may take several days of exposure to causeclinically recognizable changes. Strong irritants, for example, acidsand alkalines, cause observable changes within a few minutes. Morespecifically, allergic contact dermatitis is a delayed hypersensitivityreaction. It takes between 6 and 10 days to years for individual tobecome sensitized. Often times, ingredients in topical drugs constitutea major cause of allergic contact dermatitis. Other commonly implicatedsubstances include plants, many potential sensitisers used in themanufacture of shoes and clothing, p-phenylenediamine and other dyes andcosmetics. Contact dermatitis ranges from redness to severe swelling anditching. Any exposed skin surface in contact with the sensitizing orirritating substance may be involved.

[0009] Pemphigus is an uncommon, potentially fatal, autoimmune skindisorder characterized by bullae on apparently healthy skin and mucusmembranes that has been demonstrated to have an abnormally high pH. Theprimary lesions associated with pemphigus often occur first in themouth, where they soon rupture and remain as chronic, often painful,erosions for variable periods of time before the skin is affected. Onthe skin, the bullae typically arise from normal appearing skin to leavea raw, denuded area and crusting when they rupture later.

[0010] Dermatitis herpetiformis is a chronic eruption characterized byclusters of intensely pruritic vesicles, papules and urticaria-likelesions. With this dermatitis, itching and burning are severe, andscratching often obscures the primary lesions. This form of dermatitisis also associated with abnormally alkaline skin.

[0011] Psoriasis is a common, chronic, recurrent disease characterizedby dry, well-circumscribed, silvery, scaling papules and plaques ofvarious sizes that is associated with high alkaline skin surfaceconditions. Psoriasis varies in severity from one or two lesions to awidespread dermatitis with disabling arthritis or exfoliation. It isgenerally caused by increased epidermal cell proliferation fromabnormally alkaline stratum corneum. Psoriasis characteristicallyinvolves the scalp, the extensor surfaces of the extremities,particularly at elbows and knees and the back. The nails, eye brows andother regions may also be affected. Occasionally the disease isgeneralized.

[0012] Candidiasis, or yeast infections, may also be related to anabnormally high pH in the skin or mucous membranes. The symptoms ofcandidiasis vary from the site of the infection. However, symptomsusually include itchiness and inflammation.

[0013] Other skin disorders or pathologies that may be linked with anabnormally basic stratum corneum are acne, dermatophytosis, diaper rash,eczema and skin damage from a variety of causes including wounds, burnsand fecal and urinary incontinence. In addition, a more alkaline surfacepH has been shown to promote Staphylococcal skin colonization and theinvasion of Nector americanus, i.e. human hookworm. Alopecia, orbaldness, may also result from abnormal alkaline surface skin pH.

[0014] Many of these skin disorders or pathologies are accompanied bypruritus, a condition involving localized or general itching. Althoughusually occurring in the skin, pruritus can also occur in non-cutaneoussites such as mucous membranes. A variety of causes for the condition ofpruritus are known including external and endogenous causes, localizedskin disorders and systemic diseases. As previously discussed, manysystemic and skin diseases are accompanied by persistent or recurrentitch attacks. Itch can also be produced by a variety of chemical,mechanical, thermal and electrical stimuli.

[0015] Research into the etiology of and treatment of many skinpathologies including pruritis has been limited both by the lack ofanimal models and by patient populations that at present would notsupport the perceived research and development and clinical testingcosts. Treatment involves diagnosis of the underlying condition thatcauses pruritus and these skin disorders and pathologies and interveningtherapeutically to alleviate these conditions. For example, developmentsleading to drugs to threat these conditions have been, for the mostpart, a bonus of anti-inflammatory drugs. Such treatments are notconsidered to be direct treatments of these conditions and are oflimited efficacy, only occasionally and indirectly relieving theitching. In many cases, however, either the underlying cause for thecondition cannot be determined or cannot be eliminated. In such cases,the direct treatment of the pruritic condition or the accompanying skindisorder is required.

[0016] Generally, options for effectively treating these disorders arelimited. Currently available treatment modalities for these pathologiesinclude nonspecific topical agents such as emollients andcounterirritants, topical and oral drugs such as steroids, localanesthetics and antihistamines, and physical modalities such asultraviolet phototherapy and thermal stimulation. Some of thesetreatments are effective in pruritic conditions of a particularetiology, while others may show general but nonspecific benefit. It isknown that many corticosteroids, e.g., hydrocortisone, fluocinide,betamethasone valerate, fluocinolene acetonide, triamcinolone acetonideand others, have antiprutitic properties and may be effective intreating some skin disorders. However, prolonged use of suchcorticosteroids is associated with both cutaneous and systemic toxicside effects (e.g., fluid and electrolyte disturbances, impaired woundhealing, musculoskeletal, gastrointestinal, neurological and endocrinedisturbances) and their widespread use is limited without medicalsupervision. Selenium sulfide, sulfur and salicylic acid or tar shampoohave also been employed to treat these skin conditions. In any event,remission of the pathology or pruritus is often slow and frequentlyincomplete.

[0017] Nonspecific topical preparations can act as moisturizing lotionsor creams or as oil-based ointments that are occlusive and serve tosoften dry skin as well as provide a protective layer. While suchpreparations may have valuable moisturizing and skin softeningproperties, they also possess undesirable effects in that they generallyimpart to the skin an uncomfortable feeling of warmth in addition to asticky, oily, greasy or waxy feel. More importantly, these materialsalone have little effect, if any, on reducing itching.

[0018] Topical formulations containing pharmacologically active agentsare often useful in particular conditions but many may not be generallyuseful in all conditions. For example, topical corticosteroids are notindicated for symptomatic treatment unless a steroid responsive disorderis diagnosed.

[0019] Thus, there is a continuing need for development of new andimproved, nontoxic antipruritic and pH-adjusting agents that areeffective in treating and alleviating skin disorders, pathologies andpruritus resulting from a wide variety of causes or causes differentthan those that can be treated by currently available agents.

BRIEF SUMMARY OF THE INVENTION

[0020] The present invention provides a method of treating skinpathologies, disorders and pruritus which includes topically applying afatty acid esterified with glycerol (or another suitable alcohol) incombination with a dermatologically acceptable vehicle to adjust,regulate or control the skin pH. Examples of suitable fatty acids, asdefined herein, include, but are not limited to, acetic acid, propionicacid, butyric acid, valeric acid, caproic acid, etc. The compounds offormula (I), described hereinafter, are examples of suitable fatty acidsesterified with glycerol that can be applied to the skin to adjust pHand treat the various skin disorders described above. For example, ithas been found that the esters in accordance with the present inventioncan be applied topically at affected sites and are surprisinglytherapeutically effective such that the pruritus is rapidly andcompletely relieved.

[0021] The invention provides a simple, safe and effective way tocontrol skin pH. By normalizing abnormally alkaline skin, i.e. returningthe stratum corneum to a more typical acid milieu, many of the skindisorders and pathologies listed above can be treated. Triacetin is oneexample of a glyceryl fatty acid ester. When applied to abnormallyalkaline skin, triacetin is enzymatically hydrolyzed in the alkalinemilieu found therein to form glycerol and acetic acid. The acetate ionis a two-carbon moiety that contributes to fatty acid synthesis andultimately to tissue healing and repair. In other words, the applicationof triacetin and the other esters provide a safe way to apply an acid tonormalize the pH of the skin, and return it to its more natural acidmilieu. This results in the normalization of the pH in the stratumcorneum and subsequent skin healing. As the skin pH returns to itsnormal acidic pH, the cleavage of triacetin is halted leading to asimple control mechanism.

[0022] The compound of formula (I) is suitably the compound of formula(II) described hereinafter, which is glyceryl triacetate or 1, 2, 3propanetriol triacetate or, commonly, triacetin. It is again, notedhowever, that any of the esters described herein that is capable ofadjusting the pH of the skin will suffice. Triacetin has been used as apharmaceutical plasticizer (U.S. Pharmacopoeia National Formulary1075-76, 1492 (1985)), as an antifungal drug and a fixative in perfumery(see, The Merck Index (12^(th) ed.) p. 1636 (1996); U.S. Pat. No.3,070,497 issued to Knight), listed as one of many generalpharmaceutical carriers/diluents for primarily systemic administrationof specific compounds (see, e.g., U.S. Pat. No. 4,543,360 issued to vonAngerer et al.; U.S. Pat. No. 4,218,447 issued to Isaac et al.; U.S.Pat. No. 4,055,653 issued to Offermanns et al.; U.S. Pat. No. 4,847,297issued to Chandra; U.S. Pat. No. 5,061,700 issued to Dow et al.), as analkalinity reducing agent in permanent waving treatments for hair (see,e.g., U.S. Pat. No. 3,975,515 issued to Wajaroff et al.), and as aningredient in a vaginal tampon (see, U.S. Pat. No. 3,091,241 issued toKellett). It is noted that despite disclosure that triacetin is ageneral antifungal agent, a U.S. Food & Drug AdministrationOver-the-Counter (OTC) Drug Review Panel has concluded that there is noevidence that triacetin is effective in any fungal disease other thanthe soggy toeweb form of athlete's foot. The OTC panel also concludedthat triacetin was safe for topical use (see, Federal Register, vol. 47,12553 (Mar. 23, 1982)). It has not heretofore been known that triacetin,the compounds of formula (I) and other esterified fatty acids can beeffectively used in the treatment of pruritic conditions and other skindisorders related to pH imbalance.

[0023] The foregoing and other advantages of the present invention arerealized in one aspect thereof in a method of treating pruritus, skindisorders and skin pathologies which comprises applying a compound offormula (I) in an inert vehicle to the affected area to treat therelated skin disorder.

[0024] In another aspect, the invention provides a method of treatingskin disorders, skin pathologies and pruritus which includes applying acomposition to the pathologically or pruritically affected area, whichcomposition essentially consists of a pH modifying substance, selfregulating at the molecular level, that stabilizes the desirable healthyskin pH, namely a glyceryl fatty acid ester, e.g. a compound of formula(I).

[0025] In a further aspect, the invention provides a topicalanti-pathologic or antipruritic composition consisting of 5-100%,preferably 5-50%, by weight of a glyceryl fatty acid ester, e.g. acompound of formula (I), and 0%-95% by weight a dermatologicallyacceptable vehicle. The glyceryl fatty acid ester in accordance with thepresent invention acts as an essential active ingredient for normalizingthe skin pH to treat the skin pathology.

[0026] In yet a further aspect, the invention provides a prodrugcomposition for treating skin disorders, skin pathologies and prurituswhich consists essentially of 5-100% by weight of a glyceryl fatty acidester, e.g. a compound of formula (1), and 0%-95% by weight adermatologically acceptable vehicle.

DETAILED DESCRIPTION OF THE INVENTION

[0027] The present invention relates to a method of treating pruritusand other skin disorders which is highly effective in providing rapidand sustained relief. Accordingly, the present invention will now bedescribed in detail with respect to such endeavors. Those skilled in theart will appreciate that such a description of the invention is meant tobe exemplary only and should not be viewed as limitative of the fullscope thereof.

[0028] The term “pruritus” is meant to refer to itching which can rangefrom a mild sensation to an intense sensation of itching pain. Theitching may accompany primary skin disease or may be a symptom ofsystemic disease—sometimes the only symptom. Skin diseases in whichitching can be most severe include, among others, scabies, pediculosis,insect bites, urticaria, atopic dermatitis, contact dermatitis, lichenplanus, miliaria and dermatitis herpetiformis. Also, dry skin(especially in the elderly) is often a cause of severe generalizeditching.

[0029] The terms “skin disorder” and “skin pathology” are meant to referto and include skin conditions such as atopic dermatitis, ichthyosis,xeroderma, seborrheic dermatitis, allergic contact dermatitis, alopecia,pemphigus, dermatitis herpetiformis, psoriasis, candidiasis, acne,dermatophytosis, diaper rash, cradle cap, eczema, hookworm and skindamage from, e.g., wounds, burns, and fecal and urinary incontinence.These examples are purely illustrative and are not meant to limit thescope of the invention.

[0030] The term “compound of formula (I)” is meant to refer to thefollowing

[0031] wherein R₁, R₂ and R₃ are each independently RCOO— or H providedthat R₁, R₂ and R₃ are not all H. With regard to RCOO—, R is a saturatedor unsaturated, straight or cyclic, C₂-C₂₂ alkyl group. For saturatedfatty acids, R is suitably represented by CnH_(2n+1), such as CH₃COO—,CH₃CH₂COO— or CH₃(CH₂)₂COO—, etc. For unsaturated fatty acids, R issuitably represented by the formula C_(n)H_(2n−m), wherein n is aninteger from 1 to 23, and m is an odd integer from 1 to 7, provided thatm is less than 2n. Examples of suitable unsaturated fatty acids include,but are not limited to oleic acid, linolenic acid, linoleic acid andarachidonic acid. Positional and geometric isomers of unsaturated fattyacids are considered within the scope of formula I.

[0032] The term “fatty acid” as used herein is meant to refer tosaturated and unsaturated acids composed of a chain of alkyl groups andcharacterized by a terminal carboxyl group —COOH. Fatty acids maycontain from 2 to 24 carbon groups. The term “fatty acid” includes, butis not limited to, acetic acid, butyric acid, propionic acid, valericacid and caproic acid. The compound of formula (I) shows a variety ofboth saturated and unsaturated fatty acids.

[0033] The term “glyceryl fatty acid ester” is meant to refer to a fattyacid, as described above, esterified with glycerol.

[0034] The present invention is also suitably used for the relief ofepidermal or dermal itching associated with any condition such as asystemic disease or allergy that affect epidermal and/or dermal nerveendings, an injury resulting in localized trauma affecting the epidermalor dermal nerve endings, or localized dermatitis. In a preferred method,the invention includes a method of relief of pruritic symptomsassociated with dermatitis including actinic dermatitis, contactdermatitis such as an allergic dermatitis or contact dermatitis causedby irritating substances of plant, animal, mineral or synthetic origin.

[0035] The method of the present invention includes applying to anaffected area an effective amount of a glyceryl fatty acid ester, forexample, the compound of formula (I):

[0036] wherein R₁, R₂ and R₃ are each independently RCOO— or H providedthat R₁, R₂ and R₃ are not all H and R is a saturated or unsaturated,straight or cyclic, C₂-C₂₂ alkyl group. For saturated fatty acids, R issuitably represented by C_(n)H_(2n+1). For example, When n is 1, R₁, R₂and R₃ are each independently CH₃COO— or H. When R₁ is CH₃COO— and R₂and R₃ are H, the compound of formula (I) is glycerol monoacetate ormonacetin. When R₁ and R₂ are CH₃COO— and R₃ is H, the compound offormula (I) is glycerol diacetate or diacetin. When R₁, R₂ and R₃ areall CH₃COO—, the compound of formula (I) is glycerol triacetate ortriacetin. Triacetin or 1,2,3-propanetriol triacetate or glyceroltriacetate is given by formula (II):

[0037] Besides triacetin, diacetin and monoacetin, other esters aresuitable for adjusting skin pH, thereby treating and alleviating certainskin disorders. Other suitable fatty acids that can be esterified toglycerol include, but are not limited to, acetic acid, propionic acid,butyric acid, valeric acid and caproic acid. Again, these compounds areillustrated again by formula (1),

[0038] wherein R₁, R₂ and R₃ are each independently RCOO— or H providedthat R₁, R₂ and R₃ are not all H. With regard to RCOO—, R is a saturatedor unsaturated, straight or cyclic, C₂-C₂₂ alkyl group. For saturatedfatty acids, R is suitably represented by CnH_(2n+1). RCOO— is suitably,for example, CH₃COO—, CH₃CH₂COO— or CH₃(CH₂)₂COO—, etc. For unsaturatedfatty acids, R is suitably represented by the formula CnH_(2n−m) whereinn is an integer from 1 to 23, and m, which is the number of double bondsin R, is an odd integer from 1 to 7, provided that m is less than 2n.

[0039] Compounds of formula (I) and other esters formed from theesterification of an acid with glycerol have not previously beenrecognized as undergoing biotransformation to exhibit a desiredpharmacological effect i.e., they are, in effect, prodrugs. Thesecompounds are readily broken down by enzymes, namely esterases, presentin or on the skin, in mucus membranes and in body fluids, into glycerol(a skin protectant) and a fatty acid, which is ionized to an anion and ahydrogen ion. When R₁, R₂ and/or R₃ are CH₃COO—, for example, the esteris broken down by esterase to glycerol, acetate ion and hydrogen ion.Again, many skin disorders and pathologies are caused by abnormallyalkaline conditions in skin and membranes. The hydrogen ions tend tonormalize and return the skin pH to a more normal acidic milieu. Theaction of the esterases continues until the pH of the environment ischanged to about 4.0 to 6.0 which is the normal range for healthy skin.At this pH level, the activity of the esterases is inhibited until thepH rises again to a level where the esterases again become active. Alsopresent in the skin and other bodily environments is a protease enzymethat signals the itch sensation. This protease is also pH sensitive inthe same range, and it is believed that pH balance that is possible withapplication of compounds of formula (I) provides a dramatic andsurprising effect on pruritus.

[0040] The compounds of formula (I) are commercially available. Forexample, triacetin is commercially available in USP grade from EastmanChemical Company, Kingsport, Tenn. It is a colorless, somewhat oilyliquid with a slight fatty odor with a density at 25° C. of 1.156 g/m L.It is prepared by acetylation of glycerol. Triacetin, diacetin andmonacetin are miscible in water, alcohol, ether and chloroform.

[0041] For topical application, suitable viscous, semi-solid or solidforms can be employed which include a carrier compatible with topicalapplication. Suitable formulations include, but are not limited to,solutions, suspensions, emulsions, creams, ointments, powders,liniments, salves, sprays, aerosols and gels. Preferably, compounds offormula (I), e.g., triacetin, are formulated as an ointment in which thevehicle is Aquaphor®, commercially available from Beiersdorf Inc.,Norwalk, Conn., US. Aquaphor® is a composition of petrolatum, mineraloil, mineral wax and wool wax alcohol. Compounds of formula (I) are alsosuitably formulated as up to a 6% solution in water, and a 25% solutionin 50% alcohol, suitably isopropyl alcohol.

[0042] Optionally, the skin treating compositions of the presentinvention may suitably include auxiliary agents such as plasticizingagents, preservatives, stabilizers, demulsifiers, wetting agents,opacifiers, surfactants, fragrances, sunscreens, antibiotics, insectrepellants, preservatives, emollients, humectants, emulsifiers,thickeners, moisturizers, astringents, deodorants as well as othercompatible materials which may be desired to enhance the properties ofthe compositions.

[0043] Other suitable emollient vehicles include hydrocarbon oils andwaxes and volatile silicone fluids such a low molecular weight dimethylsiloxanes.

[0044] For topical treatment of skin disorders associated with alkalineskin pH, the concentration of the glyceryl ester in accordance with thepresent invention in a locally applied composition is about 5% to about100% by weight, preferably about 5% to about 50% by weight, i.e., about0.05 g/g to 0.5 g/g of composition, and most preferably, theconcentration is about 20% by weight. An ester concentration of 55-100%is also acceptable.

[0045] These compounds, particularly, triacetin, have been found ofvalue in the relief and treatment of pruritus due to leukoclasticvasculitis, macular; lesion from drug allergies, skin conditionsassociated with renal disease, dry skin, dandruff, anal itch, poisonivy, poison oak, poison sumac, insect bites, vaginitis, bladderinfection, diaper rash, cradle cap and eczema. Administering thesecompounds as a vaginal cream can normalize vaginal acidity. As a result,this controls and help maintain the normal healthy vaginal flora,thereby preventing bacteria and viruses that cause sexually transmitteddiseases from becoming established. These compounds of formula (I) arealso of value in treating psoriatic lesions. Triacetin has been found toimprove psoriatic lesions, applied as a topical, episodic treatment forpsoriasis. As previously discussed, these compounds can also treat andprovide relief for other skin disorders and pathologies, includingatopic dermatitis, ichthyosis, xeroderma, seborrheic dermatitis,allergic contact dermatitis, alopecia, pemphigus, dermatitisherpetiformis, psoriasis, candidiasis, acne, dermatophytosis and otherskin damage caused from a variety of wounds, burns and incontinence.

[0046] The skin treating compositions of the present invention whenapplied to the skin, e.g., up to four times per day as needed, providereduction in and relief from itching within about 24-36 hours, andrelief may even be evident after the first dose. For treatment ofpsoriasis, improvement is often seen within a day, with complete healingoccurring within about 5 to 7 days.

[0047] The skin treating composition of the present invention issuitably formulated by simply mixing the compounds of formula (I) withthe vehicle at room temperature. The composition is formulated toprovide delivery of the antipruritic compound at a suitable rate andconcentration. The composition may be in the form of any formulationthat provides the compound as bioavailable to esterase action.

[0048] The following examples are intended to illustrate, but not limit,the scope of the invention. All parts and percentages in the examplesare on a weight basis unless otherwise stated.

Medicament Preparations EXAMPLE 1

[0049] An ointment was prepared by mixing 20 g of triacetin in 80 g ofAquaphor® to yield a 20% by weight composition.

EXAMPLE 2

[0050] A topical cream is prepared by dissolving 20 g of triacetin in 40g of mineral oil and 20 g of self-emulsifying beeswax. The mixture isheated to liquefy. After the addition of 20 mL of hot water, the mixtureis mixed well. The resulting cream contains approximately 20 g oftriacetin per 100 gram of cream.

EXAMPLE 3

[0051] A dermatological lotion is prepared by dissolving 20 g oftriacetin in 80 g of dry propylene glycol. The resulting lotion containsabout 20 g of triacetin per 100 g of lotion.

EXAMPLE 4

[0052] An ointment is prepared according to Example 1 by dissolvingmonacetin.

EXAMPLE 5

[0053] An ointment is prepared according to Example 1 by dissolvingdiacetin.

Dermatological Testing EXAMPLE 6 Treatment of Pruritus

[0054] Compositions of triacetin were evaluated for therapeutic efficacyof the composition in the topical treatment of pruritus. The skintreating composition evaluated was the ointment composition prepared inExample 1. The patients were treated on an outpatient basis. Thepatients were instructed to apply the composition up to four times perday as needed.

[0055] More than 100 subjects who presented with pruritic conditionsapplied the ointment to the pruritic area up to 4 times per day asneeded. Patients were asked to note the time within which itching wasrelieved and when the symptoms wholly disappeared and reported, same toa physician. 90% of the patients reported relief from itching within24-36 hours, and 75% reported that within about 48, hours of additionaltreatment, the symptoms essentially disappeared.

EXAMPLE 7 Treatment of Psoriasis

[0056] Eight patients who presented with psoriatic lesions were treatedwith the ointment of Example 1 on an outpatient basis. The ointment ofExample 1 was applied to the psoriatic lesions up to four times per day.All patients reported to a physician improvement of the lesions withinabout a day of application, and healing within about 5-7 days.

[0057] In summary, the present invention provides a method andcomposition for treating a variety of skin disorders including pruritusand psoriasis, which includes applying glyceryl fatty acid esters,including the compounds of formula (I) in a suitable formulation to theaffected area. These compounds can also be formulated as a vaginal creamthat may be of value for controlling vaginal pH, which may prevent theestablishment of viruses such as HIV.

[0058] Many variations will suggest themselves to those skilled in theart in light of the detailed description. All such modifications andvariations are within the full intended scope of the appended claims.

What is claimed is:
 1. A method of treating skin pathologies in a humanor other mammal comprising administering to the human or mammalafflicted therewith a topical composition consisting essentially of aneffective amount of a glyceryl fatty acid ester and an inert vehicle tothe pathologically affected area.
 2. The method of claim 1, wherein theglyceryl fatty acid ester is a compound of formula (I),

wherein R₁, R₂ and R₃ are each independently RCOO— or H, provided thatR₁, R₂ and R₃ are not all H, and R is a saturated or unsaturated,straight or cyclic, C₂-C₂₂ alkyl group.
 3. The method of claim 2,wherein the saturated alkyl group is represented by CnH_(2n+1), and n isan integer from 1 to
 23. 4. The method of claim 2, wherein theunsaturated alkyl group is represented by C_(n)H_(2n−m), and n is aninteger from 1 to 23 and m is an odd integer from 1 to 7, provided thatm is less than 2n.
 5. The method of claim 3, wherein n is
 1. 6. Themethod of claim 5, wherein the compound of formula (I) is triacetin. 7.The method of claim 1, wherein the skin pathology to be treated isselected from the group consisting of psoriasis, pruritus, a psoriaticlesion, atopic dermatitis, ichthyosis, xeroderma, seborrheic dermatitis,allergic contact dermatitis, alopecia, pemphigus, dermatitisherpetiformis, psoriasis, candidiasis, acne, dermatophytosis, diaperrash, cradle cap, eczema and skin damage caused by wounds, burns orincontinence.
 8. A method of treating skin pathologies comprisingadministering topically to a human or other mammal in need thereof anamount of a composition consisting essentially of a pH modifyingsubstance and a dermatologically acceptable vehicle, said amountsufficient to normalize skin pH, said substance being a glyceryl fattyacid ester.
 9. The method of claim 8, wherein the substance is offormula (I)

wherein R₁, R₂ and R₃ are each independently RCOO— or H, provided thatR₁, R₂ and R₃ are not all H, and R is a saturated or unsaturated,straight or cyclic, C₂-C₂₂ alkyl group.
 10. The method of claim 9,wherein the saturated alkyl group is represented by CnH_(2n+1), and n isan integer from 1 to
 23. 11. The method of claim 9, wherein theunsaturated alkyl group is represented by CnH_(2n−m), and n is aninteger from 1 to 23 and m is an odd integer from 1 to 7, provided m isless than 2n.
 12. The method of claim 10, wherein n is
 1. 13. The methodof claim 12, wherein the compound of formula (I) is triacetin.
 14. Atopical composition for treating skin pathologies consisting essentiallyof 5%-100% by weight of a glyceryl fatty acid ester and 0%-95% by weightof a dermatologically acceptable vehicle, the glyceryl fatty acid esterbeing an essential active agent for normalizing the skin pH to treat theskin pathology.
 15. The composition of claim 14, wherein the glycerylfatty acid ester is a compound of formula (I)

wherein R₁, R₂ and R₃ are each independently RCOO— or H, provided thatR₁, R₂ and R₃ are not all H, and R is a saturated or unsaturated,straight or cyclic, C₂-C₂₂ alkyl group.
 16. The composition of claim 15,wherein the saturated alkyl group being represented by CnH_(2n+1), and nis an integer from 1 to
 23. 17. The composition of claim 15, wherein theunsaturated alkyl group is represented by C_(n)H_(2n−m) and n is aninteger from 1 to 23 and m is an odd integer from 1 to 7, provided thatm is less than 2n.
 18. The composition of claim 16, wherein n is
 1. 19.The composition of claim 18, wherein the compound of formula (I) istriacetin.
 20. The composition of claim 14, wherein the composition is55%-95% by weight glyceryl fatty acid ester.
 21. The composition ofclaim 14, wherein the dermatologically acceptable vehicle is apetrolatum ointment, water or alcohol.
 22. The composition of claim 14,wherein the composition is formulated as a cream, a lotion, a spray or agel.
 23. A prodrug for treating skin pathologies, the prodrug consistingessentially of 5%-100% by weight of a glyceryl fatty acid ester and0%-95% by weight of a dermatologically acceptable vehicle, wherein theglyceryl fatty acid ester is an essential active agent for normalizingthe skin pH to treat the skin pathology.
 24. The prodrug of claim 23,wherein the glyceryl fatty acid ester is a compound of formula (I)

wherein R₁, R₂ and R₃ are each independently RCOO— or H, provided thatR₁, R₂ and R₃ are not all H, and R is a saturated or unsaturated,straight or cyclic, C₂-C₂₂ alkyl group and 0%-95% by weight of adermatologically acceptable vehicle.
 25. The prodrug of claim 24,wherein the saturated alkyl group is represented by CnH_(2n+1), and n isan integer from 1 to
 23. 26. The prodrug of claim 24, wherein theunsaturated alkyl group is represented by C_(n)H_(2n−m) and n is aninteger from 1 to 23 and m is an odd integer from 1 to 7, provided thatm is less than 2n.
 27. The prodrug of claim 25, wherein n is
 1. 28. Theprodrug of claim 27, wherein the compound of formula (I) is triacetin.29. The prodrug of claim 23, wherein the prodrug is 55%-95% by weightglyceryl fatty acid ester.
 30. A pharmaceutical composition comprisingan amount of a glyceryl fatty acid ester in combination with apharmaceutically acceptable carrier, wherein said amount is effective toadjust the pH and to a normal range in an involved area of a human ormammal.
 31. The composition of claim 30, wherein the glyceryl fatty acidester is a compound of formula (I)

wherein R₁, R₂ and R₃ are each independently RCOO— or H, provided thatR₁, R₂ and R₃ are not all H, and R is a saturated or unsaturated,straight or cyclic, C₂-C₂₂ alkyl group.
 32. The composition of claim 31,wherein the saturated alkyl group is represented by CnH_(2n+1), and n isan integer from 1 to
 23. 33. The composition of claim 31, wherein theunsaturated alkyl group is represented by C_(n)H_(2n−m), and n is aninteger from 1 to 23 and m is an odd integer from 1 to 7, provided thatm is less than 2n.
 34. The composition of claim 32, wherein n is
 1. 35.The composition of claim 34, wherein the compound of formula (I) istriacetin.
 36. The composition of claim 30, wherein the composition is avaginal cream and wherein said amount is effective to increase vaginalacidity to inhibit establishment and propagation of a virus present in avagina.